The potential molecular markers of inflammatory response in KOA with AD based on single-cell transcriptome sequencing analysis and identification of ligands by virtual screening.

Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases. Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients. It was found that the higher the expression of TXNIP, MMP3, and MMP13, the higher the risk coefficient of AD was. In addition, the AUC of TXNIP, MMP3, and MMP13 were all greater than 0.70, which had good diagnostic significance for AD. Finally, through the virtual screening of core proteins in FDA drugs and molecular dynamics simulation, it was found that compound Cobicistat could be targeted to TXNIP, Itc could be targeted to MMP3, and Isavuconazonium could be targeted to MMP13. To sum up, TXNIP, MMP3, and MMP13 are prospective molecular markers in KOA with AD, which could be used to predict, diagnose, and prognosis.

Clinical observation on the treatment of displaced distal radial and ulnar fractures in children by closed manipulation combined with splinting.

Objective: The aim of this study was to investigate the clinical efficacy of closed manipulation combined with splinting in the treatment of displaced distal radial and ulnar fractures in children. Methods: A total of 82 children with displaced fractures of the distal radial and ulnar segment who met the inclusion criteria and were treated as outpatients or inpatients in the orthopedic department of Guangzhou Orthopedic Hospital, from January 2016 to June 2022 were randomly divided into an observation group and a control group: 41 children in the observation group were treated with closed manipulation combined with splint fixation; 41 children in the control group were fixed with incisional repositioning elastic nails combined with internal plates. The Anderson efficacy grading, visual analog scale (VAS) score, fracture healing time, treatment cost, hospital days, and complications were observed and compared between the two groups. Result: The efficacy was evaluated according to the Anderson forearm fracture efficacy evaluation criteria, and the results of statistical analysis showed no statistically significant differences between the two groups (P > 0.05). At 3 and 7 weeks after treatment, the VAS scores of children in both groups decreased (P < 0.05), and the VAS scores in the observation group were significantly lower than those in the control group (P < 0.05), indicating that the observation group had a significant advantage in the relief of pain after treatment. The fractures healed in both groups after treatment with the two different methods, and the difference in healing time between the two groups was not statistically significant (P > 0.05). The length of hospital stay, treatment cost, and complication ratio were significantly lower in the observation group than in the control group (P < 0.05). Conclusion: In children with displaced fractures of the distal radial and ulnar segments, treatment by manual repositioning with external splinting can achieve satisfactory results with simple operation, low cost, short hospital stay, and few complications, which is especially suitable to be promoted in primary hospitals and has good social benefits.

Tongbi Huoluo Decoction alleviates cartilage degeneration in knee osteoarthritis by inhibiting degradation of extracellular matrix.

BACKGROUND: Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA. METHODS: The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD. RESULTS: 206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC-MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion. CONCLUSION: TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA.

Bioinformatics analysis combined with molecular dynamics simulation validation to elucidate the potential molecular mechanisms of Jianshen Decoction for treatment of osteoporotic fracture.

Osteoporotic fracture (OPF) is a prevalent skeletal disease in the middle-aged and elderly. In clinical practice, Jianshen Decoction (JSD) has been used to treat OPFs. However, the specific effective components and mechanisms of JSD on OPF have not been explored. Therefore, this study used bioinformatics analysis combined with molecular dynamics simulation validation to explore the molecular mechanism of JSD treatment of OPF. Public databases (TCMSP, Batman TCM) were used to find the effective active components and corresponding target proteins of JSD (screening conditions: OB ≥ 30%, drug-likeness ≥ 0.18, half-life ≥ 4). Differentially expressed genes (DEGs) related to OPF lesions were obtained based on the gene expression omnibus database (screening conditions: adjust P value < .01, | log2 FC | ≥ 1.0). The BisoGenet plug-in and the CytoNCA plug-in of Cytoscape were used to derive the potential core target proteins of JSD in the treatment of OPF. The JSD active ingredient target interaction network and the JSD-OPF target protein core network were constructed using the Cytoscape software. In addition, the R language Bioconductor package and clusterProfiler package were used to perform gene ontology (GO)/Kyoto Encylopedia Of Genes And Genome (KEGG) enrichment analysis on core genes to explain the biological functions and signal pathways of core proteins. Finally, molecular docking and molecular dynamics simulations were carried out through PyMOL, AutoDockTools 1.5.6, Vina, LeDock, Discovery Studio (DS) 2019, and other software to verify the binding ability of drug active ingredients and core target proteins. A total of 245 targets and 70 active components were identified. Through protein-protein interaction (PPI) network construction, 39 core targets were selected for further research. GO/KEGG enrichment analysis showed that the DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, MAPK signaling pathway, and ErbB signaling pathway were mainly involved. The results of molecular docking and molecular dynamics simulations supported the good interaction between MYC protein and Quercetin/Stigmasterol. In this study, bioinformatics, molecular docking, and molecular dynamics simulations were used for the first time to clarify the active components, molecular targets, and key biological pathways of JSD in the treatment of OPF, providing a theoretical basis for further research.